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Acta Diabetologica

, Volume 51, Issue 6, pp 905–915 | Cite as

Updating the natural history of diabetic nephropathy

  • Giuseppe Pugliese
Review Article

Abstract

Diabetic nephropathy (DN) is a major cause of morbidity and mortality in patients with both types of diabetes and the leading cause of end-stage renal disease (ESRD) worldwide. The classical, five-stage natural history of DN, after an initial phase of hyperfiltration, is characterized by a progressive increase of albuminuria from normoalbuminuria to proteinuria, followed by a decline of glomerular filtration rate (GFR). Accumulating evidence indicates that clinical course of DN has changed profoundly, likely as a consequence of changes in treatment. In fact, remission/regression of microalbuminuria is a common feature of both type 1 and 2 diabetes which far outweighs progression to proteinuria. Moreover, GFR loss has been shown to occur independently of albuminuria or even in the absence of it. Nonalbuminuric renal impairment probably represents a different pathway to loss of renal function, which might recognize different pathogenic mechanisms, prognostic implications, and possibly therapeutic measures, as compared with the albuminuric pathway. The nonalbuminuric phenotype might be related to macroangiopathy instead of microangiopathy and/or be the consequence of repeated and/or unresolved episodes of acute kidney injury, even of mild degree. Reduced GFR and albuminuria are both powerful risk factor for cardiovascular events, whereas albuminuria appears to predict death and progression to ESRD better than GFR loss. Finally, it is unclear whether reduced GFR and albuminuria warrant different interventions and whether GFR decline may also regress in response to treatment, as proteinuria does. Further epidemiological, pathologic, pathophysiological, and intervention studies are needed to clarify the distinctive features of nonalbuminuric renal impairment.

Keywords

Chronic kidney disease Albuminuria GFR decline Cardiovascular disease 

Abbreviation

DN

Diabetic nephropathy

ESRD

End-stage renal disease

CVD

Cardiovascular disease

GFR

Glomerular filtration rate

BP

Blood pressure

AER

Albumin excretion rate

RAS

Renin–angiotensin system

eGFR

Estimated GFR

HbA1c

Hemoglobin A1c

TNFR

Tumor necrosis factor receptor

CKD

Chronic kidney disease

NHANES

National Health and Nutrition Examination Survey

DEMAND

Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes

UKPDS

United Kingdom Prospective Diabetes Study

DCCT/EDIC

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications

NEFRON

National Evaluation of the Frequency of Renal Impairment cO-existing with NIDDM

RIACE

Renal Insufficiency And Cardiovascular Events

PERCEDIME2

Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain

ADVANCE

Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation

FIELD

Fenofibrate Intervention and Event Lowering in Diabetes

MDRD

Modification of Diet in Renal Disease

CKD-EPI

CKD-Epidemiology Collaboration

ARIC

Atherosclerosis Risk in Communities

AKI

Acute kidney injury

KDIGO

Kidney Disease Improving Global Outcomes

RENAAL

Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan

Notes

Acknowledgments

The content of this article was the subject of the 12th Ruth Osterby Lecture, given by Professor Pugliese at the 27th Annual General Meeting of the European Diabetic Nephropathy Study Group (EDNSG), which was held in London, UK, on May 16–17, 2014. The Author thanks the RIACE Investigators for participating in the studies cited in this article. The RIACE study cited in this article was supported by the Research Foundation of the Italian Society of Diabetology (Fo.Ri.SID) and the Diabetes, Endocrinology and Metabolism (DEM) Foundation, and by unconditional grants from Eli-Lilly, Takeda, Chiesi Farmaceutici and Boehringer-Ingelheim.

Conflict of interest

None.

Human and animal rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  1. 1.Department of Clinical and Molecular Medicine“La Sapienza” University of RomeRomeItaly

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